ArticleThe Journal of experimental medicine2022
A partial form of inherited human USP18 deficiency underlies infection and inflammation.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review.The Journal of allergy and clinical immunology · 2024Pooled it
- Two novel kindreds with autosomal recessive STAT2 deficiency.Journal of human immunity · 2026Article
- Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis.The Journal of experimental medicine · 2026Article
- Familial pulmonary alveolar proteinosis and type I interferonopathy by mutation of STAT2 (TIMS2).The Journal of experimental medicine · 2026Article
- STAT2 R148 variant: A 16th-century founder mutation and clinical response to high-dose JAK inhibitor therapy.Journal of human immunity · 2026Article
- The zinc-finger protein ZC3H10 suppresses type I interferon responses during viral infection by repressing interferon-stimulated gene promoters.PLoS biology · 2026Article
- ISGylation is disrupted byiScience · 2026Article
- Human ISG15 deficiency unveils impaired healing of ulcerations via type I interferon-mediated fibrosis.Journal of human immunity · 2026Article
- IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury.Cellular and molecular life sciences : CMLS · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- Pharmacological inhibition of USP18 improves antibacterial responses and the intracellular control ofFrontiers in immunology · 2026Article
- USP18 confers protection against allergic asthma by suppressing CCL8 production in alveolar type II epithelial cells.Respiratory research · 2025Article
- Interferons in health and disease.Cell · 2025Review
- An mRNA-based broad-spectrum antiviral inspired by ISG15 deficiency protects against viral infections in vitro and in vivo.Science translational medicine · 2025Article
- Targeting USP18 overcomes acquired resistance in hepatocellular carcinoma by regulating NCOA4 deISGylation and ferroptosis.Cell death & disease · 2025Article
- Human LY9 governs CD4Science immunology · 2025Article
- Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- USP18 promote tumor immune evasion in pancreatic cancer through enhancing autolysosome-mediated degradation of MHC-I.American journal of cancer research · 2025Article
- NovelFrontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
28 authors at 6 institutions in 4 countries.
Funding
Abstract
Human USP18 is an interferon (IFN)-stimulated gene product and a negative regulator of type I IFN (IFN-I) signaling. It also removes covalently linked ISG15 from proteins, in a process called deISGylation. In turn, ISG15 prevents USP18 from being degraded by the proteasome. Autosomal recessive complete USP18 deficiency is life-threatening in infancy owing to uncontrolled IFN-I-mediated autoinflammation. We report three Moroccan siblings with autoinflammation and mycobacterial disease who are homozygous for a new USP18 variant. We demonstrate that the mutant USP18 (p.I60N) is normally stabilized by ISG15 and efficient for deISGylation but interacts poorly with the receptor-anchoring STAT2 and is impaired in negative regulation of IFN-I signaling. We also show that IFN-γ-dependent induction of IL-12 and IL-23 is reduced owing to IFN-I-mediated impairment of myeloid cells to produce both cytokines. Thus, insufficient negative regulation of IFN-I signaling by USP18-I60N underlies a specific type I interferonopathy, which impairs IL-12 and IL-23 production by myeloid cells, thereby explaining predisposition to mycobacterial disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.